A Comprehensive Monograph on the Dolutegravir/Rilpivirine Fixed-Dose Combination (Juluca®) for HIV-1 Maintenance Therapy

Executive Summary

The fixed-dose combination (FDC) of dolutegravir 50 mg and rilpivirine 25 mg, marketed as Juluca®, represents a significant evolution in the management of Human Immunodeficiency Virus Type 1 (HIV-1) infection. Its approval marked the introduction of the first complete, single-pill, two-drug regimen (2DR) for the maintenance treatment of adults with HIV-1.[1] The specific indication for this therapy is as a replacement (switch) regimen for adults who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral therapy (ART) for at least six months, with no history of treatment failure and no known or suspected resistance to either component.[3] This therapeutic strategy challenges the long-standing paradigm of three- or four-drug ART, aiming to reduce cumulative lifetime drug exposure.

The regimen's robust efficacy is rooted in its dual mechanism of action, which targets two distinct and critical stages of the HIV-1 lifecycle. Dolutegravir, a second-generation integrase strand transfer inhibitor (INSTI), prevents the integration of viral DNA into the host cell's genome, while rilpivirine, a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), blocks the conversion of viral RNA to DNA.[6] This synergistic blockade provides potent and durable viral suppression. The rationale for this 2DR is to minimize the number of antiretroviral agents a patient is exposed to over a lifetime, thereby potentially reducing the risk of long-term, cumulative drug-associated toxicities.[9]